Overall objective: To contribute to a better understanding of the hormonal regulation of calcium homeostasis as a rational basis for the prevention and medical management of calcium-related diseases, especially those occurring in old age. More specific objectives: 1. To determine the factors responsible for and the mechanisms involved in the C-cell hyperplasia and increased thyroidal and serum thyrocalcitonin (TCT) that we discovered are associated with goiters produced in rats by a low-iodine diet or propylthiouracil. What is the role of TSH (and/or TRF) and other factors? 2. To document further the relationship between age, C-cell proliferation, and increased TCT in rats, to determine at what age or ages substantial changes occur in C-cells and TCT, to determine the factors and mechanisms involved in these changes, and to evaluate their physiological and pathophysiological effects. These studies will be extended to the thyroid "dark cells". 3. To investigate further the protective effect of endogenous or injected TCT against calcification of the kidney and cardiovascular system, using a rat model in which C-cells have been removed and follicular function retained (partial thyroidectomy leaving isthmus only). The development of a second rat model, one of tertiary hyperparathyroidism, will be attempted. Methods to be employed will include radioimmunoassay of hormones, the immunoperoxidase method for specific hormone localization, and light and electron microscopy.